Screening in prevention

- Risks are involved with screening, so you may cause harm- E.g. breast screening might perform a mammectomy on a patient who has a lump that may never turn into cancer- High quality evidence for smear tests, CRC (faecal occult blood test), breast cancer- Controversial: PSA blood test for prostate cancer, MR/CR or breath test for lung cancer

Medication in prevention

- Also known as chemo-prevention- More controversial

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Primary medication in prevention

- Oesophageal cancer: high rate in parts of chine, they tried anti-oxidant supplements but there was no benefit- Breast cancer: at risk women, prophylactic tamoxifen (higher risk of getting endometrial cancer with this)

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Secondary medication in prevention

- Previous head and neck or lung cancers- Give anti-oxidant supplements- No benefit

- Gullet cancer, you can't remove it so you need to maintain function- Ear lesion, you can keep your ear with radiation therapy

5R's of radiobiology

Radiosensitivity

- How sensitive the tumour is going to be to treatment- Can anticipate outcome- Certain drugs have been proven to increase radiosensitivity

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Repair

- Radiation damages cells to a sublethal level, often the cell pathways repair themselves have been suppressed in malignant tumours- The degree of suppression will affect the repair half-life and how effective the treatment is

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Re-population

- Cells will all be in different parts of the cell cycle- S phase: typically radioresistant- Late in G2 or M phase are relatively sensitive- Idea is you catch them at some point in the cycle when they're in a more sensitive phase

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Re-oxygenation

- Tumours can be acutely or chronically hypoxic, this makes the resistant to radiation- The aim of radiation is to make them oxic as oxic cells can be killed

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Re-assortment

- Cells are in a cycle and you catch some cells at different stages, some are sensitive to radiotherapy and some aren't- G2 and M are good, late S isn't so good

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Systemic therapy

- Beneficial for widespread disease- Can result in widespread toxicity- Palliation in about 50% of cancers- Potential to be very specific- Therapeutic index: aim is to have the anti-tumour effect curve and normal tissue toxicity as far apart as possible. Separates side effects and anti-tumour effects

What are the 4 basic types of chemotherapy?

- Curative- Palliative- Adjuvant- Neoadjuvant

Curative chemotherapy

- Only about 3% of cancers, testicular, lymphomas- Can be used with radiotherapy- Important to use biomarkers to see what genes the tumours have, assess treatment methods

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Palliative therapy

- Accounts for around 50% of chemotherapy- Aim is to relieve symptoms

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Adjuvant

- When there is no longer evidence of pathology- Can reduce risk of recurrence. Based on population statistics rather than the individual

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Neoadjuvant

- Aim is to improve survival and reduce morbidity- Precedes surgery or radiotherapy- Before people have surgery to see how the cancer is going to behave and decide whether to do local or systematic therapy- Can be used to assist the surgery by ensuring cancer cells are removed in the operation and not in the bloodstream

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Immunotherapy

- Specific and non-specific types- Antibodies can target cancer, you can have a combination of mouse and human antibodies... one half of the antibody could be targeting one part and the other half of the head could be targeting another

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Types of immunotherapy

Programmed cell death pathway (PD-1)

- Uses immune system to attack 'foreign' cancer cells- Cancer hides behind inhibitors, this drug allows the immune system to see the drug- It can make things worse if you have co-morbidities- being used in lung cancer and melanoma

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Chimeric antigen receptor (CAR) T-cells

- Artificial T-cell receptors, using retroviral vectors to give a specific cell killing function directed against cancer cells- Very new- In lymphomas and leukaemias, not solid cancers- Side effects: you're taking lymphocytes out of circulation- You put them back via T cell adoptive transfer